Charcot-Marie-Tooth (CMT2D) disease is a hereditary, peripheral neuropathy caused by dominant mutations in genes encoding aminoacyl-tRNA synthetases (aaRSs)—enzymes essential for protein synthesis in all cells. Yet, the reason why these mutations primarily affect motor neurons, despite their ubiquitous expression in tissues, remains unclear. In my project, I use differentiated motor neurons derived from human stem cells to investigate how aaRS mutations associated with CMT pathology alter translation. I apply various methods such as Ribo-seq (ribosome profiling), RNA-seq, single molecule displacement mapping, cryo-ET and microscopy, biochemical analysis and AI-based predictive approaches to define common mechanisms underlying aaRS-linked neurodegeneration and to identify potential targets for therapeutic intervention in CMT.
